Development and validation of a nomogram predictive model for cognitive impairment in cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes. Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD. Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA). Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set. Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition.

Signaling pathways in brain ischemia: Mechanisms and therapeutic implications.

Ischemic stroke occurs when the arteries supplying blood to the brain are narrowed or blocked, inducing damage to brain tissue due to a lack of blood supply. One effective way to reduce brain damage and alleviate symptoms is to reopen blocked blood vessels in a timely manner and reduce neuronal damage. To achieve this, researchers have focused on identifying key cellular signaling pathways that can be targeted with drugs. These pathways include oxidative/nitrosative stress, excitatory amino acids and their receptors, inflammatory signaling molecules, metabolic pathways, ion channels, and other molecular events involved in stroke pathology. However, evidence suggests that solely focusing on protecting neurons may not yield satisfactory clinical results. Instead, researchers should consider the multifactorial and complex mechanisms underlying stroke pathology, including the interactions between different components of the neurovascular unit. Such an approach is more representative of the actual pathological process observed in clinical settings. This review summarizes recent research on the multiple molecular mechanisms and drug targets in ischemic stroke, as well as recent advances in novel therapeutic strategies. Finally, we discuss the challenges and future prospects of new strategies based on the biological characteristics of stroke.

Development and validation of a nomogram predictive model for cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a significant contributor to stroke, intracerebral hemorrhages, and vascular dementia, particularly in the elderly. Early diagnosis remains challenging. This study aimed to develop and validate a novel nomogram for the early diagnosis of cerebral small vessel disease (CSVD). We focused on integrating cerebrovascular risk factors and blood biochemical markers to identify individuals at high risk of CSVD, thus enabling early intervention. Methods: In a retrospective study conducted at the neurology department of the Affiliated Hospital of Hebei University from January 2020 to June 2022, 587 patients were enrolled. The patients were randomly divided into a training set (70%, n = 412) and a validation set (30%, n = 175). The nomogram was developed using multivariable logistic regression analysis, with variables selected through the Least Absolute Shrinkage and Selection Operator (LASSO) technique. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: Out of 88 analyzed biomarkers, 32 showed significant differences between the CSVD and non-CSVD groups. The LASSO regression identified 12 significant indicators, with nine being independent clinical predictors of CSVD. The AUC-ROC values of the nomogram were 0.849 (95% CI: 0.821-0.894) in the training set and 0.863 (95% CI: 0.810-0.917) in the validation set, indicating excellent discriminative ability. Calibration plots demonstrated good agreement between predicted and observed probabilities in both sets. DCA showed that the nomogram had significant clinical utility. Conclusions: The study successfully developed a nomogram predictive model for CSVD, incorporating nine clinical predictive factors. This model offers a valuable tool for early identification and risk assessment of CSVD, potentially enhancing clinical decision-making and patient outcomes.

A Long-Read Genome Assembly of a Native Mite in China Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae) Reveals Gene Expansion in Toxin-Related Gene Families.

Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae), discovered in China, has been demonstrated as a high-efficient natural enemy in controlling many agricultural and forestry pests. This mite injects toxins into the host (eggs, larvae, pupae, and adults), resulting in its paralyzation and then gets nourishment for reproductive development. These toxins have been approved to be mammal-safe, which have the potential to be used as biocontrol pesticides. Toxin proteins have been identified from many insects, especially those from the orders Scorpions and Araneae, some of which are now widely used as efficient biocontrol pesticides. However, toxin proteins in mites are not yet understood. In this study, we assembled the genome of P. zhonghuajia using PacBio technology and then identified toxin-related genes that are likely to be responsible for the paralytic process of P. zhonghuajia. The genome assembly has a size of 71.943 Mb, including 20 contigs with a N50 length of 21.248 Mb and a BUSCO completeness ratio of 90.6% (n = 1367). These contigs were subsequently assigned to three chromosomes. There were 11,183 protein coding genes annotated, which were assessed with 91.2% BUSCO completeness (n = 1066). Neurotoxin and dermonecrotic toxin gene families were significantly expanded within the genus of Pyemotes and they also formed several gene clusters on the chromosomes. Most of the genes from these two families and all of the three agatoxin genes were shown with higher expression in the one-day-old mites compared to the seven-day-pregnant mites, supporting that the one-day-old mites cause paralyzation and even death of the host. The identification of these toxin proteins may provide insights into how to improve the parasitism efficiency of this mite, and the purification of these proteins may be used to develop new biological pesticides.

Negative pressure promotes macrophage M1 polarization after Mycobacterium tuberculosis infection via the lncRNA XIST/microRNA-125b-5p/A20/NF-κB axis.

Experiments have demonstrated the regulation of long noncoding RNA (lncRNA) in tuberculosis (TB), and negative pressure treatment has been associated with the alleviation of TB. Here, we investigated the interaction of negative pressure and the lncRNA X-inactive specific transcript (XIST) in modulating Mycobacterium tuberculosis (MTB) infection. Initially, we established an in vitro cell model of MTB infection and an in vivo mouse model of MTB infection, followed by treatment with negative pressure. Then, we examined the expression of XIST, followed by analysis of the downstream miRNA of XIST. XIST was overexpressed or underexpressed through cell transfection to examine its effects on macrophage polarization via the miR-125b-5p/A2 axis. The MTB models were characterized by upregulated XIST and downregulated miR-125b-5p. XIST bound to miR-125b-5p, leading to its downregulation, and thus causing higher MTB survival in an ESAT-6-dependent manner. Additionally, negative pressure treatment decreased MTB-driven XIST expression through downregulation of A20 (an NF-κB repressor) via miR-125b-5 expression, promoting the M1 polarization program in macrophages through activation of the NF-κB pathway. In summary, negative pressure treatment after MTB infection can promote the polarization of macrophages to the proinflammatory M1 phenotype by regulating the XIST/miR-125b-5p/A20/NF-κB axis.

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1ß stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

Comparison of three surgical approaches for thoracolumbar junction (T12-L1) tuberculosis: a multicentre, retrospective study.

BACKGROUND: The surgical approaches to thoracolumbar junction (T12-L1) tuberculosis were controversial. We aimed to compare the safety and efficacy of three different procedures through a multicentre retrospective study. METHODS: The medical records of thoracolumbar junction tuberculosis patients (n = 177) from January 2005 to January 2015 were collected and reviewed. Forty-five patients underwent anterior debridement and instrumented fusion (Group A), 52 underwent anterior combined with posterior debridement and instrumented fusion (Group B) and 80 underwent posterior-only debridement and instrumented fusion (Group C). Patients with neurological deficit were 10 in Group A, 23 in Group B, 36 in Group C. All patients had a standard preoperative and postoperative anti - tuberculous therapy regimen. Clinical outcomes, laboratory indexes and radiological evaluation of the three groups were compared. Operations at each centre were performed by the respective senior medical teams of the six different hospitals. RESULTS: All three surgical approaches achieved bone fusion and pain relief. Cases with neurological deficits had different degrees of improvement after surgery. The operative time was 330.2 ± 45.4 min, 408.0 ± 54.3 min, 227.9 ± 58.5 min, and the blood loss was 744.0 ± 193.8 ml, 1134.6 ± 328.2 ml, 349.8 ± 289.4 ml in groups A, B and C respectively. The average loss of correction was 5.5 ± 3.7° in group A, 1.6 ± 1.9° in group B, 1.7 ± 2.2° in group C, and the difference between groups except B vs C were of statistically significant (P < 0.05). CONCLUSIONS: For patients with thoracolumbar junction (T12-L1) tuberculosis, the posterior-only procedure is the better than the anterior-only procedure in the correction of kyphosis and maintenance of spinal stability. The posterior-only procedure is recommended because it achieves the same efficacy as combined procedure with shorter operation time, less blood loss and trauma.

Surgical Treatment of Thoracic Spinal Tuberculosis: A Multicenter Retrospective Study.

OBJECTIVE: The aim of the present multicenter, retrospective study was to assess the safety and effectiveness of different surgery strategies for the treatment of thoracic tuberculosis and to provide a reference for surgical treatment of thoracic tuberculosis. MATERIALS AND METHODS: This study reviewed 394 patients with thoracic tuberculosis who were treated in 6 institutions between January 2000 and January 2015. There were 208 men and 186 women with an average age of 34.92 ± 13.14 years (range 5-76 years). A total of 73 patients underwent one-stage anterior surgery (group A); 84 underwent an anterior combined posterior surgery (group B); and 237 underwent one-stage posterior surgery (group C). Clinical outcome, laboratory indexes, and radiologic results were analyzed to observe the advantage of posterior approach surgery. RESULTS: All cases were followed up for about 26-60 months (average of 37 months). At the last follow-up, all patients reached bone fusion, pain relief, and neurologic recovery. There were significant differences before and after treatment in terms of the visual analog scale and Oswestry Disability Index scores (P < 0.05). Posterior approach significantly improved kyphosis (P < 0.05). CONCLUSIONS: Posterior fixation is superior to anterior fixation in the correction of kyphosis and maintenance of spinal stability. One-stage posterior surgery can achieve the same efficacy as anterior-only or combined surgery, with less trauma, less blood loss, and shorter operative times. However, for wide lesions or paraspinal abscesses, severe bone destruction, and anterior and middle column defects that are too large after debridement to require long segment bone grafting, the anterior combined posterior approach is indispensable.

Anterior and Posterior Instrumentation with Different Debridement and Grafting Procedures for Multi-Level Contiguous Thoracic Spinal Tuberculosis.

OBJECTIVE: To evaluate the clinical outcomes of anterior and posterior instrumentation with different debridement and graft fusion methods for multi-level contiguous thoracic spinal tuberculosis. METHODS: We retrospectively evaluated 81 patients with multi-level contiguous thoracic spinal tuberculosis who underwent anterior or posterior instrumentation combined with different methods of debridement, decompression, and graft fusion from January 2002 to December 2012. All patients were divided into an anterior instrumentation group and a posterior instrumentation group. In the anterior instrumentation group, there were 39 patients who underwent transthoracic debridement. In the posterior instrumentation group, there were 34 patients who underwent trans-costotransverse decompression and strut grafting with posterior instrumentation, and another 8 patients underwent combined anterior debridement and strut grafting with posterior instrumentation in a single-stage or two-stage procedure. The kyphotic angles were calculated from lateral spinal X-rays using the modified Konstam method. The symptoms and signs of tuberculosis, fusion level, fusion time of the bone graft, average kyphosis angle, average correction, average loss of correction, and clinical complications were recorded. The average follow-up period was 37 months (range, 17-72 months). RESULTS: The cohort consisted of 47 males and 34 females with an average age of 38 years. The mean durations of the operations were 3.5 ± 0.4 h in the anterior group and 4.0 ± 0.3 h in the posterior group ( P < 0.05). The mean blood loss volumes during surgery were 450 ± 42 and 560 ± 51 mL for the anterior group and the posterior group, respectively ( P < 0.01). The kyphotic deformities were corrected from 32.1° ± 10.3° to 10.2° ± 2.1° in the anterior group and from 33.8° ± 11.7° to 12.6° ± 2.7° in the posterior group ( P < 0.01). The neurologic statuses of the 23 patients with preoperative neurologic deficits improved in each group. Fusion was confirmed radiographically at 5.4 ± 1.2 months (range, 4-12 months) in the anterior group and 5.6 ± 1.4 months (range, 4-13 months) in the posterior group ( P > 0.05). Postoperative relapses were noted in 1 and 3 patients in the anterior and the posterior group, respectively. CONCLUSION: Posterior instrumentation was more effective than anterior instrumentation in the correction of kyphosis and the maintenance of the correction. However, postoperative sinus formation was more frequent in patients who underwent a single-stage posterior procedure.

Apelin-13 protects against apoptosis by activating AMP-activated protein kinase pathway in ischemia stroke.

Apelin has been proved to be protective against apoptosis induced by ischemic reperfusion. However, mechanisms whereby apelin produces neuroprotection remain to be elucidated. AMP-activated protein kinase (AMPK) is a master energy sensor that monitors levels of key energy metabolites. It is activated via AMPKαThr172 phosphorylation during cerebral ischemia and appears to be neuroprotective. In this study, we investigated the effect of apelin on AMPKα and tested whether apelin protecting against apoptosis was associated with AMPK signals. Focal transient cerebral ischemia/reperfusion (I/R) model in male ICR mice was induced by 60 min of ischemia followed by reperfusion. Apelin-13 was injected intracerebroventricularly 15 min before reperfusion. AMPK inhibitor, compound C, was injected to mice intraperitoneally at the onset of ischemia. In experiment 1, the effect of apelin-13 on AMPKα was measured. In experiment 2, the relevance of AMPKα and apelin-13' effect on apoptosis was measured. Data showed that apelin-13 significantly increased AMPKα phosphorylation level after cerebral I/R. Apelin-13, with the co-administration of saline, reduced apoptosis cells, down-regulated Bax and cleaved-caspase3 and up-regulated Bcl2. However, with the co-administration of compound C, apelin-13 was inefficient in affecting apoptosis and Bax, Bcl2 and cleaved-caspase3. The study provided the evidence that apelin-13 up-regulated AMPKα phosphorylation level in cerebral ischemia insults and AMPK signals participated in the mechanism of apelin-mediated neuroprotection.

Correlation of the Desialylation of Platelets with Efficacy of the First-line Therapy for ITP / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect desialylation of platelets in primary immune thrombocytopenia(ITP) patients with FITC-labelled ECL and RCA-1, and compare the correlation of the desialylation level and the efficacy of first-line therapy for ITP.</p><p><b>METHODS</b>Before treatment, 48 ITP patients were selected and their levels of ECL and RCA-1 were detected with flow cytometry.</p><p><b>RESULTS</b>The desialylation level in the different efficacy groups by using the first-line therapy of corticosteroids and (or) intravenous immunoglobulin G (IVIG) had a statistically significant difference (P<0.05). The correlation analysis showed negative relation of the therapeutic efficacy with desialylation level, that is to say, the more high of desialylation level, the more poor therapeutic efficacy of the first-line therapy.</p><p><b>CONCLUSION</b>The desialylation level of platelets in ITP patients is related with the first-line therapeutic efficacy, the efficacy for patients with high desialylation level is poor, suggesting that the FcR-independent pathway exists in clearance of platelets in ITP patients. Therefore, the desialylation level of platelets may suggest the first-line therapeutic efficacy for ITP patients to a certain degree, and may be used as a potential target for the treatment of refractory ITP.</p>

In vivo two-photon fluorescence microscopy reveals disturbed cerebral capillary blood flow and increased susceptibility to ischemic insults in diabetic mice.

AIMS: Diabetes mellitus increases the risk of stroke, but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion (MCAO) model of ischemia. METHODS: Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2-GFP mice). Four weeks later, they were subjected to transient (20 min) MCAO. In vivo blood flow was measured by two-photon laser-scanning microscopy (TPLSM) in cerebral arteries, veins, and capillaries. RESULTS: There was a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice as assessed by TPLSM, yet the regional cerebral blood flow, as assessed by laser Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation in cerebral tissues indicating disruption of the blood-brain barrier and disturbed cognitive potential. CONCLUSION: Diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.

An analysis of the Athetis lepigone transcriptome from four developmental stages.

Athetis lepigone Möschler (Lepidoptera: Noctuidae) has recently become an important insect pest of maize (Zea mays) crops in China. In order to understand the characteristics of the different developmental stages of this pest, we used Illumina short-read sequences to perform de novo transcriptome assembly and gene expression analysis for egg, larva, pupa and adult developmental stages. We obtained 10.08 Gb of raw data from Illumina sequencing and recovered 81,356 unigenes longer than 100 bp through a de novo assembly. The total sequence length reached 49.75 Mb with 858 bp of N50 and an average unigene length of 612 bp. Annotation analysis of predicted proteins indicate that 33,736 unigenes (41.47% of total unigenes) are matches to genes in the Genbank Nr database. The unigene sequences were subjected to GO, COG and KEGG functional classification. A large number of differentially expressed genes were recovered by pairwise comparison of the four developmental stages. The most dramatic differences in gene expression were found in the transitions from one stage to another stage. Some of these differentially expressed genes are related to cuticle and wing formation as well as the growth and development. We identified more than 2,500 microsatellite markers that may be used for population studies of A. lepigone. This study lays the foundation for further research on population genetics and gene function analysis in A. lepigone.

The effects of temperature on the development of the moth Athetis lepigone, and a prediction of field occurrence.

Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is an important insect pest of corn crops in China. To determine the effect of temperature on A. lepigone growth, and to provide a forecasting model for this pest, the development and fecundity of A. lepigone under five different temperatures (18, 21, 24, 27, 30 °C) was investigated, and an experimental population life table was constructed based on the obtained results. The results showed that the duration of development of A. lepigone decreased as the temperature increased from 18 to 30 °C. Approximately 95% of mature larvae stopped pupating at 18 °C, and about 70% of mature larvae stopped pupating at 21 °C. When the growth chamber temperature was above 24 °C, no growth arrest was observed. The results indicated that the optimum growth temperature of A. lepigone was about 26.47 °C. In this study, the highest survival rate, fecundity per female, and population index trend were observed when the temperature was set at 27 °C. The percentages of larvae that could spin cocoons after the 5th or 6th instar differed at the different temperatures. The developmental threshold temperatures for A. lepigone eggs, larvae, pre-pupae, pupae, preoviposition females, and the whole generation (i.e., egg to oviposition) were 11.03, 9.04, 15.08, 11.79, 11.63, and 10.84 °C, respectively, and their effective accumulative temperatures were 63.51, 339.42, 30.04, 118.41, 35.06 and 574.08 degree-days, respectively. Based on the effective accumulative temperature law, this pest insect can have four generations in most of the Huang-Huai region of China, and two to three generations annually in some cold regions. Athetis lepigone may have four generations in the mid-southern part of Hebei Province. This prediction matches the field survey results.

P2X7 signaling promotes microsphere embolism-triggered microglia activation by maintaining elevation of Fas ligand.

BACKGROUND: The cerebral microvascular occlusion elicits microvascular injury which mimics the different degrees of stroke severity observed in patients, but the mechanisms underlying these embolic injuries are far from understood. The Fas ligand (FasL)-Fas system has been implicated in a number of pathogenic states. Here, we examined the contribution of microglia-derived FasL to brain inflammatory injury, with a focus on the potential to suppress the FasL increase by inhibition of the P2X(7)-FasL signaling with pharmacological or genetic approaches during ischemia. METHODS: The cerebral microvascular occlusion was induced by microsphere injection in experimental animals. Morphological changes in microglial cells were studied immunohistochemically. The biochemical analyses were used to examine the intracellular changes of P2X(7)/FasL signaling. The BV-2 cells and primary microglia from mice genetically deficient in P2X(7) were used to further establish a linkage between microglia activation and FasL overproduction. RESULTS: The FasL expression was continuously elevated and was spatiotemporally related to microglia activation following microsphere embolism. Notably, P2X(7) expression concomitantly increased in microglia and presented a distribution pattern that was similar to that of FasL in ED1-positive cells at pathological process of microsphere embolism. Interestingly, FasL generation in cultured microglia cells subjected to oxygen-glucose deprivation-treated neuron-conditioned medium was prevented by the silencing of P2X(7). Furthermore, FasL induced the migration of BV-2 microglia, whereas the neutralization of FasL with a blocking antibody was highly effective in inhibiting ischemia-induced microglial mobility. Similar results were observed in primary microglia from wild-type mice or mice genetically deficient in P2X(7). Finally, the degrees of FasL overproduction and neuronal death were consistently reduced in P2X(7)(-/-) mice compared with wild-type littermates following microsphere embolism insult. CONCLUSION: FasL functions as a key component of an immunoreactive response loop by recruiting microglia to the lesion sites through a P2X(7)-dependent mechanism. The specific modulation of P2X(7)/FasL signaling and aberrant microglial activation could provide therapeutic benefits in acute and subacute phase of cerebral microembolic injury.

Effect of extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong on delaying aging of vascular smooth muscle cells in aged rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong (EXT) on delaying vascular smooth muscle cells (VSMCs) aging in aged rats.</p><p><b>METHODS</b>VSMCs were obtained by the modified tissue explants technique and were shown to be positive for smooth muscle α-actin (SM-α-actin) by immunohistochemistry staining. VSMCs obtained from the young rats were served as the young control group; VSMCs obtained from the old rats were treated with no drug (the old group), with low dose extracts (20 mg/L, the EXT low-concentration group) and high dose extracts (40 mg/L, the EXT high concentration group), and with Probucal (10(-6) mol/L, the Probucal group) as a positive control. All groups were cultured for 24 h in the medium with 10% serum for 24 h followed by another 24 h in the serum-free medium. At the end of the 48-h culture, the following analyses were performed including determination of senescence-associated β-galactosidase (SAβ-Gal) activity, flow cytometry analysis of cell cycle, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analyses of p16, Cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma (Rb) mRNA expression, and Western blotting analyses of p16, cyclin D1, CDK4 and phosphoretinoblastoma (pRb) protein expressions.</p><p><b>RESULTS</b>(1) In comparison to the younger rats, VSMCs from aged rats had significantly more SAβ-Gal positive cells (P<0.01) and more cells in S phase (P<0.05). VSMCs from the all treated groups showed a significant decrease in both SAβ-Gal positive cells (P<0.05) and S phase (P<0.05) compared to the old rats. (2) Compared with the young group, VSMCs in the old group had a significant decrease in p16 and Rb mRNA expression and a significant increase in Cyclin D1 and CDK4 mRNA expression. Compared with the old group, VSMCs in the treated groups had a significant increase in p16 and Rb mRNA expression and a significant decrease in Cyclin D1 and CDK4 mRNA expression (P<0.05). (3) Compared with the young group, VSMCs in the old group had a significant decrease in p16 protein expression and a significant increase in Cyclin D1, CDK4 and pRb protein expressions (P<0.05). Compared with the old group, VSMCs in the treated groups had a significant increase in p16 protein expression and a significant decrease in cyclinD1, CDK4 and pRb protein expressions (P<0.05).</p><p><b>CONCLUSIONS</b>VSMCs obtained from old rats showed typical signs of cellular senescence and vascular aging. EXT had an effect on delaying senescence of VSMCs in vitro by altering the p16-cyclinD/CDK-Rb pathway.</p>

Effect of extracts from Panax ginseng, Panax notoginseng, and Ligusticum chuanxiong on vascular smooth muscle cells of aging and hypertension rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe and compare the effects of aging and hypertension on rats' aortic vascular smooth muscle cells (VSMCs) and the effects of the extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong.</p><p><b>METHODS</b>The rat aortic VSMCs model was established using the method of primary cell culture. Of them, the rats of the aging experiment were divided into 5 groups, i.e., the young control group (as Yon), the old group (as Old), the old + probucol group (as Old+Pro), the old +low dose extracts group (as Old+Pro), and the old+high dose extracts group (as Old+High). The rats of the hypertension experiment were divided into 5 groups, i.e., the Wistar-Kyoto control group (as WKY), the spontaneously hypertensive rat group (as SHR), the SHR +Valsartan group (as SHR+Val), the SHR+low dose extracts group (as SHR+Low), and the SHR+high dose extracts group (SHR+High). The proliferation of VSMCs was detected using MTT. The expression of MMP-9 was detected by immunocytochemical assay. The mRNA and protein expressions of peroxisome proliferator activated receptor-gamma (PPAR-gamma) were detected using RT-PCR and Western blot respectively.</p><p><b>RESULTS</b>Compared with the Yon group, the proliferation of VSMCs and the MMP-9 expression increased, the mRNA and protein expressions of PPAR-gamma decreased in the Old group, all showing statistical difference (P < 0.05). Compared with the Old group, the proliferation of VSMCs and the MMP-9 expression obviously decreased, the mRNA expression of PPAR-gamma obviously increased in the Old+Pro group, the Old+High group, and the Old+Low group (all P < 0.05). The PPAR-y protein expression obviously increased in the Old+Pro group and the Old+Low group (P < 0.05). Compared with the WKY group, the proliferation of VSMCs and the expression of MMP-9 obviously increased, the mRNA and protein expressions of PPAR-gamma obviously decreased in the SHR group (all P < 0.05). Compared with the SHR group, the proliferation of VSMCs and the expression of MMP-9 obviously decreased, the mRNA and protein expressions of PPAR-gamma obviously increased in the SHR+Val group, the SHR+High group, and the SHR + Low group (all P < 0.05).</p><p><b>CONCLUSIONS</b>Both aging and hypertension could result in excessive proliferation of rat aortic VSMCs and the expression changes of correlated cytoactive factors. The extracts from Panax ginseng, Panax notoginseng (Burk.) and Ligusticum chuanxiong can lower their proliferation levels and reduce the expressions of negative cytokines, thus reducing aging and hypertension induced injury of VSMCs and delaying angiocellular aging.</p>

Comparative study on Chinese medical syndrome typing and treatment combined different surgical methods for treating clomiphene-resistant polycystic ovary syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique under laparoscope for treating clomiphene-resistant polycystic ovary syndrome (PCOS).</p><p><b>METHODS</b>Forty infertility patients with clomiphene-resistant PCOS were assigned to two groups using stratified random sampling method according to age, infertility time, and body mass index, 20 in each group. Patients in Group A were treated with Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation, while those in Group B were treated with Chinese medical syndrome typing and treatment combined unipolar electrocoagulation drilling technique. After operation Chinese herbal treatment was administered to all patients according to syndrome typing. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), androgen (T), estradiol (E2), and prolactin (PRL) were determined before and after operation. The ovulation was monitored. The pregnancy rate and the pregnancy outcomes were recorded after operation.</p><p><b>RESULTS</b>There was no statistical difference in the 3-month spontaneous ovulation rate or the 1-year pregnancy rate (P > 0.05). The levels of LH, T, and PRL were significantly lower after operation than before operation in the two groups (P < 0.05). The menstruation and ovulation were obviously improved after operation. The total ovulation rate was 95% (19/20) in Group A. Successful pregnancy occurred in 15 cases of Group A. Ovarian hyperstimulation syndrome (OHSS) occurred in 1 case of Group A. The total ovulation rate was 90% (18/20) in Group B. Successful pregnancy occurred in 13 cases of Group B. Hypovaria occurred in 1 case of Group B. Luteinized unruptured follicle (LUFS) occurred in 2 cases of Group A and 1 case of Group B.</p><p><b>CONCLUSIONS</b>Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique could effectively promote the ovulation. The two methods showed similar therapeutic effects.</p>

Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Appropriate antimicrobial therapy of community-acquired pneumonia (CAP) is mainly based on the distribution of etiology and antimicrobial resistance of major pathogens. We performed a prospective observational study of adult with CAP in 36 hospitals in China.</p><p><b>METHODS</b>Etiological pathogens were isolated in each of the centers, and all of the isolated pathogens were sent to Zhongshan Hospital for antimicrobial susceptibility tests using agar dilution.</p><p><b>RESULTS</b>A total of 593 patients were enrolled in this study, and 242 strains of bacteria were isolated from 225 patients. Streptococcus pneumoniae (79/242, 32.6%) was the most frequently isolated pathogen, followed by Haemophilus influenzae (55/242, 22.7%) and Klebsiella pneumoniae (25/242, 10.3%). Totally 527 patients underwent serological tests for atypical pathogens; Mycoplasma pneumoniae and Chlamydia pneumoniae infections were identified in 205 (38.9%) and 60 (11.4%) patients respectively. Legionella pneumophila infections were identified in 4.0% (13/324) of patients. The non-susceptibility rate of isolated Streptococcus pneumoniae to erythromycin and penicillin was 63.2% and 19.1% respectively. Six patients died from the disease, the 30-day mortality rate was 1.1% (6/533).</p><p><b>CONCLUSIONS</b>The top three bacteria responsible for CAP in Chinese adults were Streptococcus pneumonia, Haemophilus influenza and Klebsiella pneumonia. There was also a high prevalence of atypical pathogens and mixed pathogens. The resistance rates of the major isolated pathogens were relatively low except for the high prevalence of macrolide resistance in Streptococcus pneumoniae.</p>